title: Investigating the role of endogenous opioids and KATP channels in glycerol-induced acute renal failure.
abstract: The present study was designed to investigate the possible role of endogenous opioids and K(ATP) channels in glycerol-induced acute renal failure (ARF) in rats. The rats were subjected to rhabdomyolytic ARF by single intramuscular injection of hypertonic glycerol (50% v/v; 8 mL/kg), and the animals were sacrificed after 24 h of glycerol injection. The plasma creatinine, blood urea nitrogen, creatinine clearance, and histopathological studies were performed to assess the degree of renal injury. Naltrexone (2.5, 5.0 and 10.0 mg/kg s.c.), glibenclamide (5.0 and 10.0 mg/kg i.p.), and minoxidil (25 and 50 mg/kg) were employed to explore the role of endogenous opioids and K(ATP) channels in rhabdomyolysis-induced ARF. Pretreatment with naltrexone and glibenclamide attenuated hypertonic glycerol-induced renal dysfunction in a dose-dependent manner, suggesting the role of endogenous opioids and K(ATP) channels in the pathogenesis of myoglobuniric renal failure. However, the simultaneous pretreatment with naltrexone (10 mg/kg s.c.) and glibenclamide (10 mg/kg i.p.) did not enhance the reno-protective effects of individual drugs, suggesting that release of endogenous opioids and opening of K(ATP) channels constitute a single pathway in acute renal injury triggered by hypertonic glycerol-induced rhabdomyolysis. Furthermore, administration of minoxidil abolished the attenuating effects of naltrexone in glycerol-induced renal failure, suggesting that opening of K(ATP) channels is downstream to opioid receptor activation. It is concluded that hypertonic glycerol-induced rhabdomyolysis may involve release of endogenous opioids that in turn modulate K(ATP) channels to contribute in the pathogenesis of ARF.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, Punjab, India.
authors.forename: Dharmraj Singh
authors.initials: DS
authors.lastname: Sauriyal
authors.forename: Amteshwar Singh
authors.initials: AS
authors.lastname: Jaggi
authors.forename: Nirmal
authors.initials: N
authors.lastname: Singh
authors.forename: Arunachalam
authors.initials: A
authors.lastname: Muthuraman
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000378:metabolism*; D000818:Animals; D001806:Blood Urea Nitrogen; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D005990:Glycerol / Q000633:toxicity*; D008297:Male; D009271:Naltrexone / Q000494:pharmacology; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018847:Opioid Peptides; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D009271:Naltrexone; D005990:Glycerol; D005905:Glyburide